Tenacissoside H Induces Autophagy and Radiosensitivity of Hepatocellular Carcinoma Cells by PI3K/Akt/mTOR Signaling Pathway.

Tenacissoside H Induces Autophagy and Radiosensitivity of Hepatocellular Carcinoma Cells by PI3K/Akt/mTOR Signaling Pathway.
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Tenacissoside H通过PI3K/AKT/MTOR信号通路诱导肝细胞癌细胞的自噬和放射敏性。

DOI:
10.1177/15593258211011023
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发表时间:
2021-04
期刊:
Dose-response : a publication of International Hormesis Society
影响因子:
--
通讯作者:
Yu H
Yu H
中科院分区:
其他
文献类型:
--
作者:
Lin J;Ruan J;Zhu H;Chen Z;Chen J;Yu H

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Tenacissoside H (TEH)是从马蹄草茎中提取的主要活性成分,具有抗炎和抗肿瘤作用。然而,TEH对肝细胞癌(HCC)的作用及其潜在机制尚不清楚。目前,HCC细胞(包括Huh-7和HepG2)用不同浓度的TEH处理。通过细胞计数试剂盒-8 (CCK8)和流式细胞术检测肝癌细胞的增殖和凋亡情况。Western blot检测细胞自噬和凋亡相关蛋白的表达。采用组织免疫荧光法检测LC3B在肿瘤组织中的表达。结果表明,TEH对肝癌细胞的生长具有浓度依赖性。此外,TEH还能增强肝癌细胞的放射敏感性,促进其凋亡。此外,TEH显著提高了自噬相关基因(LC3-II/LC2-I、ATG5、Beclin-1)的mRNA和蛋白水平。在机制上,TEH减弱了PI3K/Akt/mTOR信号通路的激活。然而,抑制pi3k通路可消除TEH在HCC细胞中的抗肿瘤作用。综上所述,本研究提示TEH通过下调PI3K/Akt/mTOR信号通路诱导肝癌细胞自噬和凋亡,从而提高肝癌细胞的放射敏感性。
Tenacissoside H (TEH), which has anti-inflammatory and anti-tumor effects, is a major active ingredient extracted from the stem of Marsdenia tenacissima. However, the effect of TEH on hepatocellular carcinoma (HCC) as well as the underlying mechanisms are still indistinct. Presently, HCC cells (including Huh-7 and HepG2) were dealt with different concentrations of TEH. The proliferation and apoptosis of HCC cells were determined via Cell Counting Kit-8 (CCK8) assay and flow cytometry. In addition, Western blot was conducted to evaluate the expressions of autophagy—and apoptosis-related proteins. Tissue immunofluorescence was carried out to evaluate LC3B expression in the tumor tissues. The data showed that TEH suppressed the growth of HCC cells in a concentration-dependent manner. Besides, TEH enhanced radiosensitivity and promoted the apoptosis of HCC cells. Moreover, the mRNA and protein levels of autophagy-related genes (LC3-II/LC2-I, ATG5, Beclin-1) were significantly promoted by TEH. Mechanistically, TEH attenuated the activation of PI3K/Akt/mTOR signaling pathway. However, inhibition of PI3 K pathway abolished the anti-tumor effects of TEH in HCC cells. Collectively, this study suggested that TEH increases the radiosensitivity of HCC cells via inducing autophagy and apoptosis through downregulating PI3K/Akt/mTOR signaling pathway.
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